PDF(Pubmed)
Abstract：
The neurotrophin nerve growth factor (NGF) and its precursor proNGF are both bioactive and exert similar or opposite actions depending on the cell target and its milieu. The balance between NGF and proNGF is crucial for cell and tissue homeostasis and it is considered an indicator of pathological conditions. Proteolytical cleavage of proNGF to the mature form results in different fragments, whose function and/or bioactivity is still unclear. The present study was conducted to investigate the distribution of proNGF fragments derived from endogenous cleavage in brain and peripheral tissues of adult rats in the healthy condition and following inflammatory lipopolysaccharide (LPS) challenge. Different anti-proNGF antibodies were tested and the presence of short peptides corresponding to the prodomain sequence (pdNGFpep) was identified. Processing of proNGF was found to be tissue-specific and accumulation of pdNGFpeps was found in inflamed tissues, mainly in testis, intestine and heart, suggesting a possible correlation between organ functions and a response to insults and/or injury. The bioactivity of pdNGFpep was also demonstrated in vitro by using primary hippocampal neurons. Our study supports a biological function for the NGF precursor prodomain and indicates that short peptides from residues 1-60, differing from the 70-110 sequence, induce apoptosis, thereby opening the way for identification of new molecular targets to study pathological conditions.
摘要：
神经营养蛋白神经生长因子（NGF）及其前体proNGF均具有生物活性，并根据细胞靶标及其环境发挥相似或相反的作用。NGF和proNGF之间的平衡对于细胞和组织稳态至关重要，并且被认为是病理状况的指标。proNGF到成熟形式的蛋白水解切割产生不同的片段，其功能和/或生物活性尚不清楚。进行本研究是为了研究在健康状态下和炎性脂多糖（LPS）攻击后，内源性裂解产生的proNGF片段在成年大鼠脑和外周组织中的分布。测试了不同的抗-proNGF抗体,并鉴定了对应于前结构域序列(pdNGFpep)的短肽的存在。发现proNGF的加工是组织特异性的，并且在发炎的组织中发现了pdNGFpeps的积累，主要在睾丸,肠和心脏，提示器官功能与对侮辱和/或损伤的反应之间可能存在相关性。通过使用原代海马神经元在体外也证明了pdNGFpep的生物活性。我们的研究支持NGF前体前结构域的生物学功能，并表明来自残基1-60的短肽，不同于70-110序列，诱导细胞凋亡，从而为鉴定新的分子靶标以研究病理状况开辟了道路。
